Challenges and unanswered questions for the next decade of circulating tumour cell research in lung cancer

Mohan, Sumitra; Chemi, Francesca; Brady, Ged

doi:10.21037/tlcr.2017.06.04

Cited by 29 publications

(26 citation statements)

References 175 publications

(177 reference statements)

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“…The sensitive, specific detection and enumeration of CTCs remains a challenge in patients with NSCLC; however, this is still a developing field, with no universal method of detection suitable for all types of cancer. 16,17 Currently, a more mature technology commercially available for identifying CTCs from the blood of cancer patients is CellSearch, which uses immunomagnetic beads 18,19 ; other capture technologies, including array scanning, functionalized micro-nanostructured surfaces, microfluidic micro-mixers, etc are also being developed and applied. 20 Among them, immunochemical-based beads or nanoparticles can recognize and capture CTCs in whole blood with high efficiency and high selectivity.…”

Section: Discussionmentioning

confidence: 99%

Sorting and gene mutation verification of circulating tumor cells of lung cancer with epidermal growth factor receptor peptide lipid magnetic spheres

Wang

Zhang

et al. 2020

Thoracic Cancer

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Background: This study aimed to identify an efficient, simple, and specific method of detecting mutations in the epidermal growth factor receptor (EGFR) gene in isolated lung cancer circulating tumor cells (CTCs) and to improve the ability to obtain tumor tissue clinically. Methods: EGFR peptide lipid magnetic spheres (EG-P-LMB) were prepared by reverse evaporation, and characterization and cell capture efficiency assessed. The peripheral blood samples of 30 lung cancer patients were isolated and identified with the EG-P-LMB using 20 healthy volunteers as controls. Finally, the isolated CTCs were tested for EGFR gene mutations, and the tissue samples selected for comparison. Results: The prepared magnetic spheres had a smaller particle size and higher stability according to the particle size potential test. Their morphology was homogeneous by atomic force observation, and the UV test showed that there were peptides on the surface. The separation efficiency of EG-P-LMB was greater than 90% in PBS and greater than 80% in the blood simulation system. Compared with the tissue sample results, the positive rate of EGFR gene mutations was 94%. The CTC test results of 27 patients were consistent with the tissue test results of the corresponding patients, and the consistency with the tissue comparison test results was 90% (27/30). Conclusions: EG-P-LMB can effectively capture CTCs in the peripheral blood of patients with lung cancer. CTC detection can accurately identify mutations in the EGFR gene and improve the ability to obtain tumor tissue in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Sorting and gene mutation verification of circulating tumor cells of lung cancer with epidermal growth factor receptor peptide lipid magnetic spheres

Wang

Zhang

et al. 2020

Thoracic Cancer

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“…Even if in the large majority of cases, the EGFR mutations are detected in an automatized manner from DNA extracted from plasma, these mutations have also been found in CTCs [ 44 , 45 ]. However, currently, despite numerous promises that have emerged from this specific domain of LB, this application is not used in a daily routine practice for EGFR mutational assessment and no automatized test has been approved to date for this by the FDA [ 46 ]. Different reasons can explain this limited interest in using CTCs as a possible target for determination of the EGFR mutation status: the difficulty of using a sensitive and specific method for CTC detection, the small number of CTCs in blood samples, and the phenotypic variabilities of CTCs, in particular due to the epithelio-mesenchyma transition phenomena [ 46 , 47 ].…”

Section: Mutations In Egfr: the Main Therapeutic Target Examined Imentioning

confidence: 99%

Liquid Biopsy and Therapeutic Targets: Present and Future Issues in Thoracic Oncology

Hofman

2017

Cancers

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The practice of liquid biopsy (LB) has revolutionized the care of patients with metastatic lung cancer. Many oncologists now use this approach in daily practice, applying precise procedures for the detection of activating or resistance mutations in EGFR. These tests are performed with plasma DNA and have been approved as companion diagnostic test for patients treated with tyrosine kinase inhibitors. ALK is another important target in lung cancer since it leads to treatment of patients who are positive for a rearrangement in ALK identified with tumor tissue. By analogy with EGFR, LB for detection of genomic alterations in ALK (rearrangements or mutations) has been rapidly adopted in the clinic. However, this promising approach has some limitations and has not yet been disseminated as much as the blood test targeting EGFR. In addition to these two therapeutic targets LB can be used for evaluation of the genomic status of other genes of interest of patients with lung cancer (ROS1, RET, NTRK MET, BRAF, HER2, etc.). LB can be performed to evaluate a specific target or for a more or less complex panel of genes. Considering the number of potential targets for clinical trials, techniques of next-generation sequencing of circulating DNA are on the rise. This review will provide an update on the contribution of LB to care of patients with metastatic lung cancer, including the present limits of this approach, and will consider certain perspectives.

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“…Consequently CTCs are widely considered as one of the most promising biomarkers for hematogenous metastases (2). Due to the extreme rarity of CTCs and the epithelial nature of many cancers, the epithelial cell adhesion molecule (EpCAM) and different members of cytokeratin (CK) family are currently employed for candidate CTC enrichment and identification, prior to subsequent characterization (3)(4)(5). The EpCAM/CK-based detection strategy has been adopted by the most commonly used, FDA-cleared CellSearch system for CTC enumeration, although this procedure has intrinsic limitations in detecting CTCs from non-epithelial malignancies (4).…”

Section: Introductionmentioning

confidence: 99%

“…Due to the extreme rarity of CTCs and the epithelial nature of many cancers, the epithelial cell adhesion molecule (EpCAM) and different members of cytokeratin (CK) family are currently employed for candidate CTC enrichment and identification, prior to subsequent characterization (3)(4)(5). The EpCAM/CK-based detection strategy has been adopted by the most commonly used, FDA-cleared CellSearch system for CTC enumeration, although this procedure has intrinsic limitations in detecting CTCs from non-epithelial malignancies (4). Although the CellSearch system provides reliable performance in breast, prostate, and colorectal cancers (3,4), CTCs are much less frequently observed in peripheral blood of non-small cell lung cancer (NSCLC) patients when compared to other epithelial cancers using EpCAM/CK-based methods, despite the highly aggressive nature of NSCLC (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…The EpCAM/CK-based detection strategy has been adopted by the most commonly used, FDA-cleared CellSearch system for CTC enumeration, although this procedure has intrinsic limitations in detecting CTCs from non-epithelial malignancies (4). Although the CellSearch system provides reliable performance in breast, prostate, and colorectal cancers (3,4), CTCs are much less frequently observed in peripheral blood of non-small cell lung cancer (NSCLC) patients when compared to other epithelial cancers using EpCAM/CK-based methods, despite the highly aggressive nature of NSCLC (5)(6)(7)(8). Previous studies reported that less than 5 CTCs were detected in 7.5 mL blood in a majority (~85%) of stage IV NSCLC patients, and essentially no CTCs were detected in the blood from early stage patients with localized NSCLC disease (6,8).…”

Section: Introductionmentioning

confidence: 99%

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Resolving an underrepresented circulating tumor cell population in lung cancer enabled by Hexokinase 2 analysis

Liu

Yan

Chen

et al. 2020

Preprint

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Unlike other epithelial cancer types, circulating tumor cells (CTCs) are less frequently detected in the peripheral blood of non-small cell lung cancer (NSCLC) patients using epithelial marker-based detection approaches, despite the aggressive nature of NSCLC. Here we demonstrate hexokinase-2 (HK2) as a metabolic function-associated marker for detection of CTCs, with significantly improved detection rates and high specificity, in 33 NSCLC patients. Use of the HK2 marker identified underrepresented cytokeratin-negative (HK2 high /CK neg ) CTCs present in many blood samples but rarely detected in pleural effusions or cerebrospinal fluids of NSCLC patients.HK2 high /CK neg CTCs exhibited smaller sizes but consistent copy number variation profiles compared to CK pos CTCs. Surprisingly, CK expression levels were found to be independent of CTC epithelial-to-mesenchymal transition (EMT) status as measured by single-cell transcriptome profiling, challenging the long-standing association between CK expression and EMT. Our approach improves sensitivity of CTC detection in NSCLC and can potentially resolve a more complete spectrum of CTCs, regardless of their CK expression levels or epithelial traits.

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Challenges and unanswered questions for the next decade of circulating tumour cell research in lung cancer

Cited by 29 publications

References 175 publications

Sorting and gene mutation verification of circulating tumor cells of lung cancer with epidermal growth factor receptor peptide lipid magnetic spheres

Sorting and gene mutation verification of circulating tumor cells of lung cancer with epidermal growth factor receptor peptide lipid magnetic spheres

Liquid Biopsy and Therapeutic Targets: Present and Future Issues in Thoracic Oncology

Resolving an underrepresented circulating tumor cell population in lung cancer enabled by Hexokinase 2 analysis

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